Malaria Genetics Section
Dr. Wellems focuses on the determinants of drug resistance, immune evasion, and disease virulence in malaria. Areas of study include the antimalarial drug resistance and factors that affect clinical outcome after treatment, malaria protection conferred by human hemoglobinopathies and other red cell polymorphisms, antigenic variation by Plasmodium falciparum parasites, and molecular mechanisms of malaria parasite infectivity and pathogenesis. Research activities on the NIH campus are integrated with field studies in Africa and Southeast Asia.
Apicomplexan Molecular Physiology Section
Dr. Desai’s group studies the molecular and cellular biology of malaria parasite adaptation to intracellular growth within erythrocytes. His studies have identified two unusual ion channels that play a central role in nutrient and ion transport between plasma and parasite compartments. One of these channels, the plasmodial surface anion channel (PSAC), is exposed on the infected erythrocyte surface and is being actively pursued as an antimalarial drug target.
Malaria Cell Biology Section
Dr. Miller’s study of the pathogenesis of malaria includes research on the mechanism by which malaria parasites invade erythrocytes, including the study of parasite ligands and erythrocyte receptors; the mechanism of antigenic variation; the molecular basis for cerebral malaria and rosetting; and the binding of var gene products to endothelium.
Malaria Functional Genomics Section
Dr. Su’s laboratory develops and uses genetic and genomic approaches to study host-malaria parasite interaction and molecular mechanisms of the interaction using the rodent malaria parasite Plasmodium yoelii as a model. He has characterized large numbers of microsatellites and single nucleotide polymorphisms (SNPs) from several P. yoelii parasites and performed various genetic crosses to identify parasite genes linked to parasite development, virulence, and drug resistance. He is studying host immune signaling pathways in response to parasite infections, focusing on innate signaling and regulation of type I interferon production and inflammatory responses after malaria infection. He is also interested in anti-malarial drug screening and mechanism of drug resistance.
Joel Vega Rodriguez
Molecular Parasitology and Entomology Unit
Dr. Vega-Rodriguez’s group, the Molecular Parasitology and Entomology Unit, LMVR/NIAID/NIH, studies the biology of the malaria parasite during sexual reproduction in the mosquito and during sporozoite transmission, by characterizing essential vector-parasite and host-parasite interactions. Areas of study include the role of vector and host factors for sporozoite infectivity, and molecular mechanisms required for Plasmodium sexual reproduction. The main goal is to identify new targets for malaria interventions including chemotherapy, vaccines, and transgenic mosquitoes. We use a combination of molecular, cellular, and entomological technologies including single-cell transcriptomics, proteomics, parasite and mosquito transgenesis, RNA interference, and microscopy.
Malaria Immunity and Pathogenesis
Pathogenesis and Immunity Section
Dr. Duffy conducts human and animal studies of malaria pathogenesis and host immunity, including population-based studies in African communities exposed to Plasmodium falciparum, and controlled human infection studies. His natural history studies emphasize mechanisms of immunopathogenesis in pregnant women and children, as well as community-wide studies of malaria transmission, with large collaborative cohort studies in progress in Mali and elsewhere. His controlled human infection studies at the Clinical Center and in the field seek to understand immunity against preerythrocytic parasites and to model parasite transmission to mosquitoes. He directs the intramural malaria vaccine program at NIAID, which leads the world in clinical development of transmission-blocking vaccines, studies whole sporozoite vaccines in humans, and is designing vaccine candidates against placental malaria and severe childhood malaria.
Molecular Pathogenesis and Biomarkers Section
Dr. Fried applies functional genomics and molecular immunoparasitology tools to understand malaria pathogenesis in naturally exposed individuals. Her goal is to identify malaria biomarkers and candidate vaccine antigens that may be useful in developing new interventions. Major areas of research include correlates of immunity: parasite adhesion phenotypes, parasite antigens, and antigen specific antibodies; disease biomarkers: pathways analysis of host response and disease comparison; and identifying targets of pre-erythrocytic immunity.
Lymphocyte Activation Section
Dr. Pierce works to understand the cellular mechanisms underlying the generation, maintenance, and activation of B cell immunological memory. These studies are focused on the acquisition and maintenance of memory in response to antigens of the malaria parasite Plasmodium falciparum, in response to vaccination in the United States and to natural infection in Africa.
Malaria Infection Biology and Immunity Unit
In the Malaria Infection Biology and Immunity Unit (MIBIU), we aim to fill the critical knowledge gap about the poorly understood nature of the immune response that confers protection against malaria by applying recent advances in immunology and genomics-based technology to carefully conducted longitudinal cohort studies in malaria-endemic areas. Ultimately, an improved understanding of the human immune response to P. falciparum infection is likely to provide key insights into how malaria immunity can be enhanced through vaccination.
Chemotaxis Signal Section
The research in Dr. Jin’s laboratory is focused on understanding the cellular and molecular mechanisms underlying chemotaxis of eukaryotes. His research strategy to define the signaling network controlling chemotaxis relies on the use of the genetically amendable model organism Dictyostelium discoideum. He is developing cutting-edge live cell imaging technologies that visualize signaling events in live cells in real time, constructing computational models to comprehend the signaling network as a system, and discovering novel mechanisms involving G-protein-coupled receptor (GPCR)-mediated cell migration.
Molecular and Cellular Immunology Section
Dr. Long’s section studies the biochemical and cellular basis for regulation of natural killer (NK) cells, with an emphasis on receptors that activate or inhibit NK cell reactivity. His lab is dissecting the response of human NK cells to Plasmodium parasite infection at the blood stage and how it may contribute to protective immunity. Together with Peter Crompton, he is analyzing NK cells from a cohort of individuals living in a malaria-endemic area.
Autoimmunity and Functional Genomics Section
Dr. Bolland is interested in immune inhibitory pathways and their role in preventing autoimmunity. Major areas of research include identification of new genetic modifiers of systemic autoimmune disease, dose effect of Toll-like receptor genes and its role in autoimmune pathologies, and inhibitory signaling pathways mediated by the IgG Fc receptor (Fc gamma RIIB) and the phosphoinositol 5-phosphatase (SHIP).
Dr. Ackerman's Physiology Unit LMVR/NIAID/NIH, studies blood flow dysregulation in the human red blood cell diseases malaria and sickle cell anemia. Our goal is to understand how inherited and acquired conditions that decrease hemoglobin synthesis, e.g., alpha thalassemia and iron deficiency, improve the outcome of malaria or sickle cell disease. With this knowledge, we aim to develop new treatments for the vascular complications of these common global diseases.
Niraj Harish Tolia, Ph.D.
Host-Pathogen Interactions and Structural Vaccinology Section
The Tolia laboratory has pioneered the structural and biophysical studies of host-pathogen interactions, antibody neutralization and immunogen design for malaria. A major goal is to define how processes required for malaria parasite survival are mediated and can be exploited for preventative, therapeutic and diagnostic purposes. This work has direct implications for drug and vaccine development. His laboratory uses the tools of microbiology, cell biology, biochemistry, biophysics and structural biology to study proteins and complexes.
Malaria Immunology Section
Dr. Long focuses on analysis of the interface between the malaria parasite and the immune system of the vertebrate host. Her studies are directed toward a better understanding of these complex and important parasites, particularly the sexual stages responsible for transmission. Her laboratory is involved in identification and evaluation of possible candidate antigens for a malaria vaccine. She is studying the acquisition of clinical immunity in children living in malaria-endemic areas and she has a long-standing collaboration with investigators in Mali, West Africa.
Mosquito Immunity and Vector Competence Section
Dr. Barillas-Mury investigates the interactions between Plasmodium parasites, the gut microbiota, and the mosquito immune system to understand how they affect malaria transmission. She studies epithelial immunity, hemocyte differentiation, immune memory and the immune pathways that mediate antiplasmodial responses in the mosquito, and how Plasmodium ;evades these mosquito defense responses. Her ultimate goal is to identify new targets to disrupt malaria transmission and prevent human disease.
Malaria Culture and Insectary Unit
Dr. Lehmann's research explores broad population biology questions relevant to patterns of malaria transmission and vector control. We are studying the ecology of mosquitoes, addressing questions relevant to patterns of malaria transmission and vector control. Together with colleagues in Mali and elsewhere, we investigate the role of dormancy and long-range migration in the persistence of mosquitoes and malaria in seasonally arid areas, the processes affecting spread of genes within and between populations, and vector-parasite interactions at the population level. The nature of these topics within the One Health paradigm demands novel and creative approaches to answer stubborn old questions and identify new ones. Thus, we combine ecological, behavioral, physiological, genetic, and molecular analyses grounded in field studies to improve understanding of phenotypic diversity in vectors and its epidemiological consequences. The research group is nested in the Malaria Culture and Insectary Unit/Office of the Chief, LMVR/NIAID/NIH under Dr. Thomas Wellems.
Molecular Entomology Unit
The overall objective of Dr. Calvo’s research in the Molecular Entomology Unit, LMVR/NIAID/NIH, is to gain new insights into the role of mosquito salivary molecules in the transmission and infection of malaria parasites and other vector—borne pathogens. Avian and murine models of malaria transmission are currently used in his lab. Dr. Calvo aims to develop new transmission-blocking strategies for vector-borne diseases. A combination of assay development and gene editing (based on the CRISPR/Cas9 system) are being used to accomplish this goal.